Editor's Note: The European Society for Medical Oncology (ESMO) Annual Meeting was held in Barcelona, Spain. At this prestigious conference, Dr. Yanhong Deng from the Sixth Affiliated Hospital, Sun Yat-sen University presented findings on the efficacy of Ivonescimab, with or without Ligufalimab, combined with FOLFOXIRI as first-line treatment for metastatic colorectal cancer (mCRC) (Abstract No: 514MO). Oncology Frontier Digestive Updates had the privilege of an exclusive interview with Dr. Deng for an in-depth analysis of this study.Oncology Frontier: Could you briefly introduce the current first-line treatment landscape for mCRC and the background of your study design?
Dr. Yanhong Deng: The first-line treatment strategy for mCRC is primarily determined by the tumor’s mismatch repair (MMR) status and RAS gene mutations (including KRAS and NRAS). At this year’s ESMO meeting, we noticed a trend toward more refined early-stage research for mCRC treatment, particularly targeting specific subtypes like BRAF-mutated or HER2-overexpressing mCRC patients. This reflects a growing interest in exploring personalized treatment strategies beyond just MMR and RAS status.
In our study, we deliberately excluded patients with deficient mismatch repair (dMMR) and instead included all other molecular subtypes. This decision was based on two key considerations.
First, the triplet chemotherapy regimen we employed is known for its high-intensity therapeutic effect, which is critical in colorectal cancer treatment. We believe that using the most effective treatment as first-line therapy can provide surgical opportunities for previously unresectable cases and even turn potentially incurable conditions into curable ones. For this reason, we advocate for a triplet chemotherapy regimen as the first-line standard.
Second, immunotherapy and anti-angiogenesis treatments are two pivotal strategies in colorectal cancer management. Our study combined these two therapeutic modalities with triplet chemotherapy, achieving impressive results. This integrated approach proved effective for both RAS-mutant and RAS wild-type patients, regardless of their BRAF mutation status.
Looking ahead, while targeted strategies for specific molecular subtypes like BRAF V600E or HER2-positive mCRC may be necessary, starting with a broadly applicable first-line treatment and then tailoring maintenance strategies based on individual patient profiles seems to align with the overarching treatment trends.
Oncology Frontier: Your study demonstrated promising efficacy and tolerability with Ivonescimab, with or without Ligufalimab, combined with FOLFOXIRI as first-line treatment for mCRC. Could you elaborate on the main findings, their clinical significance, and how this approach compares to the current first-line standard?
Dr. Yanhong Deng: The main outcomes of our study focused on objective response rate (ORR), progression-free survival (PFS), and adverse events. Ivonescimab combined with FOLFOXIRI showed significant efficacy as a first-line treatment for mCRC, particularly in microsatellite-stable (MSS) mCRC patients. The ORR reached 81.8% with the Ivonescimab-FOLFOXIRI combination, and when Ligufalimab was added, the ORR further improved to 88%. Compared to the current standard treatments, these response rates represent a marked improvement.
Additionally, it’s worth noting that 90% of patients in the study had synchronous metastases, and 80% had liver metastases—patient populations traditionally considered less responsive to PD-1 inhibitors. This makes our findings highly clinically relevant for these challenging cases.
While the PFS data is not yet fully mature, preliminary results show that the 9-month PFS rate exceeded 80% in both groups, with the median PFS expected to surpass one year. In terms of safety, adverse events were mainly chemotherapy-related, such as leukopenia and nausea/vomiting, with very low rates of immune-related adverse events. These results suggest that the Ivonescimab-based regimen improves efficacy while maintaining tolerable safety.
Oncology Frontier: Your study included treatment-naive MSS mCRC patients, some of whom had KRAS or BRAF mutations. Could you discuss the advantages of this treatment regimen for specific patient groups and whether it’s suitable for mCRC patients who have already undergone systemic therapy? How do KRAS and BRAF mutations impact treatment outcomes?
Dr. Yanhong Deng: Our study included treatment-naive MSS mCRC patients, including those with KRAS or BRAF mutations. Initial analyses revealed no significant differences in efficacy between patients with or without these mutations when treated with the Ivonescimab-FOLFOXIRI regimen. This indicates that the treatment may be effective even in patients with these challenging mutations.
We also observed that RAS wild-type patients might derive even greater benefit from this combination therapy, though this warrants further exploration in future studies. Notably, 90% of the patients enrolled in our study had synchronous metastases and had not received prior treatment, which allowed us to observe their unaltered response to therapy. Remarkably, we observed tumor shrinkage in 100% of these patients—an encouraging sign of the regimen’s potential.
Oncology Frontier: Based on your findings, what directions should future research in mCRC treatment take? What are your next research plans?
Dr. Yanhong Deng: Our research highlights several key directions for the future of mCRC treatment. First, as our understanding of tumor molecular characteristics deepens, future strategies will increasingly focus on tailoring therapies to specific genetic mutations, such as KRAS G12C, NRAS, or HER2 amplification.
Second, our findings suggest that the combined regimen we employed has broad efficacy in unselected mCRC patient populations. Future studies should aim to validate these results across larger patient cohorts and explore stratified treatment approaches based on molecular subtypes.
Moreover, there is significant potential in exploring maintenance therapies following first-line treatment to prolong patient survival. Our next steps involve advancing this study to a phase III clinical trial to further confirm the efficacy and safety of this regimen under broader clinical conditions.
Oncology Frontier: Among the studies presented at this year’s ESMO conference, which ones left the strongest impression on you?
Dr. Yanhong Deng: This year’s ESMO conference featured many groundbreaking studies, especially in the field of mCRC treatment. Our session on lower gastrointestinal tumors included eight studies, and I’m proud that our team’s research received high praise from attending experts and sparked lively discussions. These studies reflect China’s growing prominence in the development of bispecific antibodies and novel immunotherapies.
One particularly noteworthy study investigated a bispecific antibody targeting EGFR and cMET, achieving an impressive efficacy rate close to 90%. This study points to an important direction for future treatment strategies in colorectal cancer.
I was also excited by research on organ-preservation strategies. Though these studies involved small sample sizes, they offer a glimpse into new treatment possibilities. In rectal cancer, achieving complete tumor remission through drug therapy and radiotherapy allows patients to enter a watch-and-wait phase, leading to an organ preservation rate of up to 80%. This has profound implications for improving patients’ quality of life.
As someone specializing in rectal cancer research, I’m acutely aware of the importance of preserving organ function for nearly 70% of rectal cancer patients facing challenges with anal preservation. If we can enhance treatment efficacy to achieve organ and functional preservation, it will be a tremendous benefit for patients. Our team is actively pursuing research in this area to improve outcomes for early-stage rectal cancer patients.
Overall, this year’s conference emphasized quality of life as a central theme, and I’m delighted to see Chinese research aligning with global trends and offering hope for patients.
